Division of Urology, University of São Paulo Medical School, Hospital das Clínicas de São Paulo, Av Enéas de Carvalho Aguiar, 255, São Paulo, SP, 05403-000, Brazil.
Faculdade Atenas, Campos Passos, Rua Oscar Cândido Monteiro, 1000, Passos, MG, 37900-380, Brazil.
World J Urol. 2021 Feb;39(2):453-459. doi: 10.1007/s00345-020-03188-x. Epub 2020 Apr 6.
To perform a feasibility phase study of a panel of putative protein biomarkers and determine whether it can identify and predict tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC) on follow-up.
We prospectively analyzed the urine of 152 patients previously treated for NMIBC. Quantitative expression of plasminogen activator inhibitor-1 (PAI-1), DJ-1, apolipoprotein A-I (apoA-1), matrix metallopeptidase-9 (MMP-9), and interleukin-8 (IL-8) was assessed by enzyme-linked immunosorbent assay and compared amongst patients with and without bladder cancer recurrence at urine collection and during 3 years of follow-up. Tumor recurrence was confirmed by pathologic analysis. We performed a prediction analysis, excluding patients with recurrence at the start of the study, and assessed the influence of previous use of intravesical BCG on the level of biomarkers.
Median follow-up time was 47 months (interquartile range 39-50 months). Sixteen patients (10.5%) were diagnosed with recurrence at the start of the study, and 21 (15.4%) were diagnosed during the study. Three biomarker proteins (apoA-1, MMP-9, and IL-8) appear to hold diagnostic potential [odds ratio (OR) = 12.9; 95% CI 3.5-47.4]; while, PAI-1 and IL-8 predict recurrence (OR = 4.1; 95% CI 1.4-11.4). Previous use of intravesical BCG did not affect biomarker levels.
In the feasibility phase, the panel of urine biomarkers analyzed detected and predicted recurrence of NMIBC and provided reliable results in patients who had previously used intravesical BCG. Validation studies are required to confirm the panel clinical utility.
对一组假定的蛋白质生物标志物进行可行性阶段研究，并确定其是否能够在随访中识别和预测非肌层浸润性膀胱癌（NMIBC）患者的肿瘤复发。
我们前瞻性分析了 152 例先前接受 NMIBC 治疗的患者的尿液。通过酶联免疫吸附试验（ELISA）评估尿纤溶酶原激活物抑制剂-1（PAI-1）、DJ-1、载脂蛋白 A-I（apoA-1）、基质金属蛋白酶-9（MMP-9）和白细胞介素-8（IL-8）的定量表达，并在尿液采集时以及 3 年随访期间比较有和无膀胱癌复发的患者之间的差异。肿瘤复发通过病理分析确认。我们进行了预测分析，排除研究开始时复发的患者，并评估了既往膀胱内 BCG 应用对生物标志物水平的影响。
中位随访时间为 47 个月（四分位距 39-50 个月）。16 例（10.5%）患者在研究开始时被诊断为复发，21 例（15.4%）在研究期间被诊断为复发。三种生物标志物蛋白（apoA-1、MMP-9 和 IL-8）似乎具有诊断潜力[比值比（OR）=12.9；95%置信区间 3.5-47.4]；而 PAI-1 和 IL-8 则预测复发（OR=4.1；95%置信区间 1.4-11.4）。既往膀胱内 BCG 应用并不影响生物标志物水平。
在可行性阶段，分析的尿液生物标志物组合检测并预测了 NMIBC 的复发，并为先前使用过膀胱内 BCG 的患者提供了可靠的结果。需要验证研究来确认该生物标志物组合的临床实用性。
